Delayed-onset cytomegalovirus disease coded during hospital readmission in a multicenter, retrospective cohort of liver transplant recipients

Delayed-onset cytomegalovirus (CMV) disease can occur among liver transplant recipients after CMV prophylaxis is stopped. We hypothesized that delayed-onset CMV disease (>100 days after transplant) occurs more commonly than early-onset CMV disease and is associated with clinical sepsis and death. Using 2004-2010 International Classification of Diseases, Ninth Revision, Clinical Modification billing data from 4 Healthcare Cost and Utilization Project state inpatient databases, we assembled a large and more representative cohort of 7229 adult liver transplant recipients from 26 transplant centers, and we identified demographics, comorbidities, CMV disease, and clinical sepsis coded during readmission and inpatient death. Multivariate analysis was performed with Cox proportional hazards models. Delayed-onset CMV disease occurred in 4.3% (n = 309), whereas early-onset CMV disease occurred in 2% (n = 142). Delayed-onset CMV disease was associated with previous transplant failure or rejection [adjusted hazard ratio (aHR), 1.4; 95% confidence interval (CI), 1.1-1.7]. Clinical sepsis > 100 days after transplant was associated with previous CMV disease (aHR, 1.3; 95% CI; 1.0-1.7), previous transplant failure or rejection (aHR, 2.1; 95% CI; 1.8-2.4), female sex (aHR, 1.3; 95% CI; 1.1-1.5), and several comorbidities. Death > 100 days after transplant was associated with delayed-onset CMV disease (aHR, 2.0; 95% CI; 1.6-2.6), transplant failure or rejection (aHR, 4.3; 95% CI; 3.4-5.5), increasing age by decade (aHR, 1.1; 95% CI; 1.0-1.2), and some comorbidities. In conclusion, delayed-onset CMV disease is more common than early-onset CMV disease among liver transplant recipients. Previous CMV disease may be a risk factor for clinical sepsis > 100 days after transplant, and delayed-onset CMV disease may be a risk factor for death > 100 days after transplant.